Acute Pharmacokinetic and Pharmacodynamic Effects of "Tobacco-Free" Oral Nicotine Pouches in Smokers

Drug Effect Clinical Trial

Official title:

Acute Pharmacokinetic and Pharmacodynamic Effects of "Tobacco-Free" Oral Nicotine Pouches in Smokers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05335915
• Other study ID #: IRB00318560
• Secondary ID: 1R01DA055962-01
• Status: Recruiting
• Phase: Phase 1
• Start date: July 27, 2022
• Est. completion date: September 1, 2025

Study information

• Verified date: December 2023
• Source: Johns Hopkins University
• Contact: Tory Spindle, PhD
• Phone: 410-550-0529
• Email: tspindle[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the present study is to examine the pharmacokinetics and pharmacodynamics of "tobacco-free" oral nicotine pouches, at various doses and flavors, in healthy adult smokers. The study will utilize a within-subjects, double-blind design. Upon enrollment, participants will complete 7 dosing conditions: tobacco-flavored pouch (low or high nicotine dose), mint/menthol-flavored pouch (low or high nicotine dose), and fruit-flavored pouch (low or high nicotine dose); participants will also complete a condition where the participants will smoke participants' preferred brand of cigarettes. In each experimental session, participants will complete 2 product-use bouts. In bout 1, the participants will use a single product (pouch or cigarette) for a fixed period under controlled conditions. In bout 2, participants will be given 2 hours to use participants' assigned product ad libitum.

Description:

The purpose of the present study is to examine the pharmacokinetics and pharmacodynamics of "tobacco-free" oral nicotine pouches, at various doses and flavors, in healthy adult smokers. The study will utilize a within-subjects, double-blind design. Upon enrollment, participants will complete 7 dosing conditions: tobacco-flavored pouch (low or high nicotine dose), mint/menthol-flavored pouch (low or high nicotine dose), and fruit-flavored pouch (low or high nicotine dose); participants will also complete a condition where the participants will smoke participants' preferred brand of cigarettes. In each experimental session, participants will complete 2 product-use bouts. In bout 1, the participants will use a single product (pouch or cigarette) for a fixed period under controlled conditions. In bout 2, participants will be given 2 hours to use participants' assigned product ad libitum. Blood specimens will be obtained throughout the sessions to characterize the pharmacokinetics of nicotine and various pharmacodynamic outcomes (subjective drug effects, tobacco withdrawal symptoms, vital signs) will also be assessed. These procedures will be completed 7 separate times (on separate visits) by each participant (sessions will be separated by at least 48 hours).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: September 1, 2025
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

1. = 21 years old

2. good general health based on screening procedures (e.g., physical exam, blood testing)

3. vital signs in normal range (resting heart rate less than 100bpm, systolic blood pressure less than 150mmHg, diastolic blood pressure less than 90mmHg)

4. negative urine test for illicit drug use (excluding THC) and negative breath alcohol test at screening and before each session

5. self-report currently smoking daily

6. self-report at least a one year history of regular smoking

7. exhaled breath CO greater than or equal to 10ppm and urine cotinine greater than 100 ng/ml at screening

8. meet criteria for at least mild tobacco use disorder

9. no self-reported regular use of other tobacco products (e.g., smokeless products, e-cigarettes) in the past 30 days

10. no self-reported prior use of novel oral nicotine pouches

11. exhaled breath CO less than 10 ppm upon arrival for each study session.

Exclusion Criteria:

1. Psychoactive drug use (aside from cannabis, nicotine, alcohol, or caffeine) in past month

2. Current use of over-the-counter (OTC) drugs, supplements/vitamins, or prescription medications that, in the opinion of the investigators or medical staff, will impact safety

3. Use of cannabis >4 times per week

4. History of or current significant medical condition that, in the opinion of the investigators or medical staff, will impact safety

5. Current psychiatric condition or substance use disorder (aside from tobacco use disorder) that, in the opinion of the investigators or medical staff, will impact safety or study outcomes

6. Women who are pregnant, planning to become pregnant, or are breast-feeding

7. Currently seeking treatment to quit smoking or currently using a nicotine/tobacco cessation product.

8. Enrollment in another clinical trial in the past 30 days

Related Conditions & MeSH terms

• Drug Effect
• Nicotine Addiction
• Nicotine Withdrawal
• Tobacco Use Disorder

Intervention

Other:
• Nicotine
Nicotine pouches will be self-administered
• Cigarette
Cigarette will be smoked

Locations

Country	Name	City	State
United States	Johns Hopkins Behavioral Pharmacology Research Unit	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics of nicotine as assessed by the Cmax	Blood plasma samples will be collected and sent to a designated laboratory for quantitative analysis of nicotine. Maximum concentration (Cmax), is the highest plasma nicotine concentration reached during a session and provides important insight into the abuse liability of a tobacco product.	Up to 6.5 hours
Primary	Pharmacokinetics of nicotine as assessed by the AUC	Blood plasma samples will be collected and sent to a designated laboratory for quantitative analysis of nicotine. Area under the curve (AUC), represents the total nicotine exposure during an entire session and provides important insight into the abuse liability of a tobacco product.	Up to 6.5 hours
Primary	Subjective ratings of "Like Drug Effect" as assessed by the Drug Effect Questionnaire	The DEQ will be used to obtain subjective ratings of "like drug effect". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	6.5 hours
Primary	Subjective ratings of "Pleasant Drug Effect" as assessed by the Drug Effect Questionnaire	The DEQ will be used to obtain subjective ratings of "pleasant drug effect". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	6.5 hours
Primary	Subjective ratings of "take again" as assessed by the Drug Effect Questionnaire	The DEQ will be used to obtain subjective ratings of "take again". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	6.5 hours
Primary	Subjective ratings of "urge to smoke" as assessed by the Hughes-Hatsukami Withdrawal Questionnaire	The HHWS will be used to obtain subjective ratings of "urge to smoke". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	6.5 hours
Primary	Subjective ratings of "craving to smoke" as assessed by the Hughes-Hatsukami Withdrawal Questionnaire	The HHWS will be used to obtain subjective ratings of "craving to smoke". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	6.5 hours
Secondary	Pharmacokinetics of nicotine as assessed by the Tmax	Blood plasma samples will be collected and sent to a designated laboratory for quantitative analysis of nicotine. Time to maximum concentration (Tmax), is the time (in minutes) to reach Cmax. This is another measure relevant for abuse liability.	Up to 6.5 hours
Secondary	Tobacco withdrawal symptoms as assessed by the Tiffany-Drobes QSU brief-Factor 1	The QSU-brief factor 1 (intention to smoke) measures tobacco withdrawal symptoms using 5 items; scores are summed to produce a single score ranging from 0 to 30	6.5 hours
Secondary	Tobacco withdrawal symptoms as assessed by the Tiffany-Drobes QSU brief-Factor 2	The QSU-brief factor 2 (anticipation of relief) measures tobacco withdrawal symptoms using 5 items; scores are summed to produce a single score ranging from 0 to 24	6.5 hours
Secondary	Topography as assessed by the total time of use	During the 2 hour ad libitum bout, topography will be collected. The total time of use (out of 2 hours) will be assessed.	2 hours
Secondary	The Direct Effects of Nicotine Scale (DENS)	The DENS will assess nicotine-specific effects. Scores range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	6.5 hours
Secondary	Perceived strength of effects as assessed by the Drug Effect Questionnaire	The DEQ will assess subjective ratings for "feel drug effect". Scores range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	6.5 hours
Secondary	Negative and aversive effects as assessed by the Drug Effect Questionnaire	The DEQ will assess subjective ratings for "dislike drug effect". Scores range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	6.5 hours